title: At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation.
abstract: BACKGROUND
  Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).
  
  
  METHODS
  In a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.
  
  
  RESULTS
  Serum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R(2) = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.
  
  
  CONCLUSIONS
  A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.
authors.affiliation: Dorothy M, Davis Heart and Lung Research Institute, The Ohio State University, 473 W 12th Ave, Suite 200, Columbus, OH 43210, USA. raman.1@osu.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Chang
authors.forename: Tam
authors.initials: T
authors.lastname: Tran
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
authors.forename: Mark W
authors.initials: MW
authors.lastname: Julian
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hamlin
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.forename: Peter B
authors.initials: PB
authors.lastname: Baker
authors.forename: Guohong
authors.initials: G
authors.lastname: Shao
authors.forename: Elliott D
authors.initials: ED
authors.lastname: Crouser
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D019069:Cell Respiration; D004195:Disease Models, Animal; D004285:Dogs; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D008279:Magnetic Resonance Imaging; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D058958:Organs at Risk; D010101:Oxygen Consumption; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013318:Stroke Volume; D013997:Time Factors; D014022:Tissue Survival; D019210:Troponin I / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D019210:Troponin I; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2